Effects of Prefrontal Repetitive Transcranial Magnetic Stimulation on Executive Function in Veterans with Parkinson’s Disease and Mild Cognitive Impairment
Alexandria Umbarger1, Sandra Kletzel1, Blake McReavy1, Sadie Walker1, Miloni Shah1, Rama Alsakaji1, Kalea Colletta1
1Edward Hines Jr. VA Hospital
Objective:

Describe preliminary cognitive effects of 10 sessions of high frequency rTMS targeted to the left dorsolateral prefrontal cortex (DLPFC) in Veterans with PD-MCI.

Background:

Executive function impairment is a hallmark symptom of Parkinson’s disease (PD). This includes dysfunction in tasks such as trial and error learning, planning, response monitoring and set shifting. Longitudinal studies indicate that 20-55% of PD patients currently have mild cognitive impairment (PD-MCI); up to 80% may develop dementia (PD-D). There is paucity of effective treatments addressing cognitive decline. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive approach to modulate brain activity. rTMS is an FDA-approved treatment for depression and research indicates a potential utility for cognitive enhancement in neurodegenerative diseases.

Design/Methods:

Veterans with PD-MCI were enrolled in a randomized control trial. rTMS was targeted with neuronavigation to the left DLPFC. 15Hz rTMS was delivered at 110% resting motor threshold (5sec/train, 40 trains/session). Neuropsychological assessments were collected pre and post intervention and at 1-month follow-up. The primary outcome was the NIH-sponsored Executive Abilities: Measures and Instruments for neurobehavioral evaluation and research (NIH-EXAMINER) executive composite score. Safety measures were collected before and after each TMS session.

Results:

Ten Veterans with PD-MCI were randomized into the active (n=6) or placebo (n=4) group. All ten Veterans completed baseline, endpoint and follow-up measures. Preliminary analysis indicates no difference between the two groups for the NIH-EXAMINER.  Baseline executive function scores were generally lower in the control group; both groups demonstrated improvement in executive function. There was no change in depression, apathy, or anxiety outcomes. Covariates, such as age, baseline mood, and medications were not considered in this analysis.

Conclusions:
The rTMS intervention was safe and feasible for Veterans with PD-MCI.  Cognitive improvements occurred in both active and placebo groups; placebo effects should be carefully considered. Covariates and factors that mediate treatment responsiveness should be investigated. 
10.1212/WNL.0000000000206644